Regulator of ephrin-Eph receptor signaling and mouse having abnormal ephrin-Eph receptor signaling mechanisms

Abstract

It is intended to provide an agent for regulating axon extension during neuranagenesis by regulating ephrin-Eph receptor signaling mechanisms and to provide a mouse having abnormal ephrin-Eph receptor signaling mechanisms. The present invention relates to a regulator of axon extension, comprising an agent for promoting or suppressing the function of α-chimerin, and to a miffy (mfy) mouse derived from a B6 strain, which displays autosomal recessive inheritance of an abnormal walking trait exhibiting a hopping gait with left-right synchronized movement of limbs and has mutation in an α-chimerin gene.

Description

BACKGROUND OF THE INVENTION[0001]1. Field of the Invention[0002]The present invention relates to the regulation of ephrin-Eph receptor signaling mechanisms. Particularly, the present invention relates to the regulation of ephrinB3-EphA4 signaling mechanisms by targeting α-chimerin (α-chimaerin) in the signaling mechanisms.[0003]2. Background Art[0004]Ephrins are cell surface-bound proteins and are ligands for Eph receptors. Ephrin / Eph binding induces bidirectional signaling (see Noren, N. K. et al., (2004) Cell Signal. 16, 655-666 and Palmer, A. et al, (2003) Genes Dev. 17, 1429-1450). Ephrin / Eph signaling, which functions in short-range cell-to-cell communication usually through repulsive effects, plays a central role in neuronal circuit formation (see Palmer, A. et al, (2003) Genes Dev. 17, 1429-1450, Flanagan, J. G. et al., (1998) Annu. Rev. Neurosci. 21, 309-345, and Pasquale, E. B. (2005), Nat. Rev. Mol. Cell Biol. 6, 462-475). Downstream signaling mechanisms have been studied ...

AI Technical Summary

Benefits of technology

[0009]The present inventor analyzed the corticospinal tract using mfy. In wild-type mice, the right brain controls movements in the left side of the body, while the left brain controls movements in the right side of the body. Axons extending from the left and right cerebral motor cortexes cross the midline at the medulla, then descend the white matter in the contralateral spinal cord, and enter the grey matter at their respective required sites. Then, they form direct or indirect synaptic connection with peripheral motor neurons that regulate muscle movement. In this process, once the axons cross the spinal cord midline, they are prevented from crossing back (i.e., re-crossing) the midline. The present inventor analyzed the corticospinal tract of mfy using a tracer and consequently found that many axons re-cross the spinal cord midline.

Problems solved by technology

However, its downstream mechanisms are poorly understood.

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